It is well-known that malignantly transformed cells often display aberrant levels and types of surface glycosylation, a feature which serves to characteristically differentiate tumor cells from normal, healthy cells. This abnormal glycosylation pattern on the tumor cell surface provides a potential opportunity for tumor immunologists to develop carbohydrate-based anticancer vaccines for cancer therapeutic treatment. Proper exposure of vaccine constructs containing tumor-associated carbohydrate antigens to the immune system would stimulate the formation of corresponding antibodies. These antibodies, in turn, would selectively bind and help eradicate tumor cells overexpressing those carbohydrate epitopes.
Toward this end, synthetic chemists and cancer immunologists have been striving to develop effective carbohydrate-based anticancer vaccines for cancer immunotherapy. In recent years, important advances in this field have been reported by others (Ingale, S.; Wolfert, M. A.; Gaekwad, J.; Buskas, T.; Boons, G.-J. Nat. Chem. Biol. 2007, 3, 663; Buskas, T.; Ingale, S.; Boons, G.-J. Angew. Chem., Int. Ed. 2005, 44, 5985; Kunz, H.; Dziadek, S.; Wittrock, S.; Becker, T. ACS Symposium Series 2008, 989 (Carbohydrate-Based Vaccines), 293; Westerlind, U.; Hobel, A.; Gaidzik, N.; Schmitt, E.; Kunz, H. Angew. Chem., Int. Ed. 2008, 47, 7551; Wittrock, S.; Becker, T.; Kunz, H. Angew. Chem., Int. Ed. 2007, 46, 5226-5230; Dziadek, S.; Brocke, C.; Kunz, H. Chem. Eur. J. 2004, 10, 4150; Hermans, I. F.; Silk, J. D.; Gileadi, U.; Salio, M.; Mathew, B.; Ritter, G.; Schmidt, R.; Harris, Adrian L.; Old, L.; Cerundolo, V. J. Immunol. 2003, 171, 5140; Schmidt, R. R.; Castro-Palomino, J. C.; Retz, O. Pure Appl. Chem. 1999, 71, 729), as well as by Applicant (Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem. Int. Ed. Engl. 1996, 35, 1380; Danishefsky, S. J.; Allen, J. R. Angew. Chem. Int. Ed. Engl. 2000, 39, 836; Keding, S. J.; Danishefsky, S. J. Carbohydrate-Based Drug Discovery 2003, 1, 381; Warren, J. D.; Geng, X.; Danishefsky, S. J. Top. Curr. Chem. 2007, 267, 109).
Although several synthetic constructs have been developed in recent years, as described above, and in other references described herein, there remains a need for the further investigation to develop novel constructs capable of eliciting a more sustained or effective (and preferably selective) immune response. Clearly, in an effort to achieve this goal, it would be useful to develop new compositions and methods for inducing an immunogenic response as well as improved and/or novel methods for the treatment of cancer.